The purpose of the present proposal is to strengthen and expand the research programs in metabolic regulation and neoplasia in the Laboratory for Experimental Oncology. The individual research projects include investigations of (1) regulation of metabolism and cellular proliferation in mammalian cells, (2) enzyme pattern-directed experimental chemotherapy of hepatomas and renal cell carcinomas, (3) regulation of purine degradation and salvage pathways, (4) regulation of key enzymes of IMP biosynthesis and degradation in normal and neoplastic cells, (5) control of thymidine metabolism, (6) somatic cell hybridization in elucidation of the role of metabolic imbalance in neoplastic transformation and progression, and (7) karyotype and chromosome banding pattern and enzymology in hepatomas and in somatic cell hybrids. These investigations are directed to elucidate the control of gene expression as manifested in the altered metabolic regulation in neoplasia.